- Standardization according to International Scale (IS)
- The established methodology to calculate and validate conversion factors by sending aliquots of 30 patient samples (10-20 million leukocytes in 1mL Trizol) on dry ice. The samples should have been collected in your institution within 3 months representing the following distribution of BCR-ABL expression: n=10 samples with 0.01%-0.1%, n=10 samples with 0.1%-1% and n=10 samples with 1%-10% BCR-ABL. After RNA extraction, cDNA synthesis and duplicate PCR for BCR-ABL and housekeeping genes the results will be compared with your local results and evaluated concerning concordance with the reference results. Following our algorithm (Müller et al., Leukemia 2009) a conversion factor can be calculated or validated using the Bland-Altman-Bias plot. Depending on the stability of the conversion factor and the degree of concordance of the results, this strategy should be repeated after 6 or 12 months. Changes in local procedures would only be advisable if samples do not meet minimum quality criteria.
- Alternatively a run-specific conversion factor could be calculated and supervised by using proposed plasmid standards as well as calibrators aligned to the primary WHO BCR-ABL standard. This strategy would obviate sample exchanges as mentioned above. Every run should either be disclosed to IHO by comfortable upload to our web server online (permanent connection) or by offline upload in a case-by-case fashion (no permanent connection to IHO, system must be installed locally in your laboratory).
- Laboratory information system (LIS) for management of laboratory results and patient data, graphical follow-up, report management
- In case you only wish to use a potent LIS, programmed with modern language (PHP), field-tested in laboratories with more than 110.000 samples dealing with more than 320.000 results. Our LIS integrates patient data, clinical information, external results (e.g. cytogenetic or FISH results), comfortable graphical follow-up, report management (available as pdf, e.g. for referring hematologists). Permanent online support, no need to locally install LIS using the online system
- The above mentioned can alternatively be locally installed at your local data center, maintenance will primarily being managed by local IT support.
- Consulting for the improvement of BCR-ABL diagnostics (e.g. improve sensitivity for MR4.5 monitoring, protocol checks, workflow/process optimization)
- Measuring deep molecular response is becoming more and more critical for properly determining suitable patients being eligible for tyrosine kinase inhibitor treatment discontinuation trials. Within the next few years more and more patients will stop treatment referring to published data of stopping trials. Without taking care about utmost high sensitivity in BCR-ABL negative samples there is a high risk of misinterpretation, e.g. over-estimation of deep molecular response, which endangers patients who will subsequently stop TKI treatment. Currently it is anticipated that BCR-ABL labs should achieve MR4.5 sensitivity in the median of all samples measured. That means that using a comparable plasmid as reference material, one should achieve a median of more than 32.000 ABL copies per PCR reaction. If this is not the case in your laboratory, we might help you improve the sensitivity by checking your protocols and advise by recommending changes in your workflow and processes.
- Quality management concerns (certification/accreditation according to DIN EN ISO 15189:2014)
- Leading an accredited laboratory we can consult you in approaching accreditation according to DIN EN ISO 15189:2014 by making use of our experience with this cumbersome process.
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